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BackgroundDuring the first SARS-CoV-2 pandemic phase, the sudden closure of schools was one of the main measures to minimize the spread of the virus. In the second phase, several safety procedures were implemented to avoid school closure.To evaluate if the school is a safe place, students and staff of two school complexes of Rome were monitored to evaluate the efficacy of prevention measures inside the school buildings.MethodsOral secretions specimens were collected from 1262 subjects for a total of 3431 samples, collected over a 3 months period.Detection of Coronavirus SARS-CoV-2 was performed by real-time PCR. Target genes were represented by E gene, RdRP/S gene and N gene.ResultsAmong the 3431 samples analyzed, just 16 sample resulted as positive or low positive: 1 sample in the first month, 12 samples in the second month and 3 in the third month.In each period of evaluation, all positive children attended different classes.ConclusionsEven if the school has the potential for spreading viruses, our preliminary results show the efficacy of the implementations undertaken in this setting to minimize virus diffusion.Our evidence suggests that school does not act as an amplifier for transmission of SARS-CoV-2 and can be really considered a safe place for students.

Healthcare expenditure is on the rise placing greater emphasis on operational excellence, cost containment, and high quality of care. Significant variation is seen in operating room (OR) costs with common surgical procedures such as laparoscopic appendectomy. Surgeons can influence cost through the selection of instrumentation for common surgical procedures such as laparoscopic appendectomy. We aimed to quantify the cost of laparoscopic appendectomy in our healthcare system and compare cost variations to operative times and outcomes. We performed a retrospective review of laparoscopic appendectomies in a large regional healthcare system during one-year period (2018). Operating room supply costs and procedure durations were obtained for each hospital. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) outcomes and demographics were compared to the costs for each hospital. A total of 4757 laparoscopic appendectomies were performed at 20 hospitals (27 to 522 per hospital) by 233 surgeons. The average supply cost per case ranged from $650 to $1067. Individual surgeon cost ranged from $197 to $1181. The average operative time was 41 min (range 33 to 60 min). There was no association between lower cost and longer operative time. The patient demographics and comorbidities were similar between sites. There were no significant differences in postoperative complications between high- and low-cost centers. The items with the greatest increase in cost were single-use energy devices (SUD) and endoscopic stapler. We estimate that a saving of over $417 per case is possible by avoiding the use of energy devices and may be as high as $ 984 by adding selective use of staplers. These modifications would result in an annual savings of $1 million for our health system and more than $ 125 million nationwide. Performing laparoscopic appendectomy with reusable instruments and finding alternatives to expensive energy devices and staplers can significantly decrease costs and does not increase operative time or postoperative complications.

Background: Extrapulmonary tuberculosis (EPTB) remains difficult to diagnose because the clinical specimens to be examined are often paucibacillary and obtained with difficulty from inaccessible sites. An updated Xpert&reg MTB/RIF Ultra (Ultra) test has been designed and licensed to improve sensitivity in the detection of Mycobacterium tuberculosis complex. The aim of the present study is to evaluate the performance of Ultra assay for the clinical diagnosis of EPTB in a low tuberculosis prevalence country. Methods: A retrospective analysis was performed at “A. O dei Colli” of Naples on consecutive extrapulmonary specimens for EPTB across a three-year period. All different types of extrapulmonary specimens were tested for EPTB by smear microscopy, culture and Ultra assay in accordance with relevant guidelines. Results: A total of 606 EPTB samples, 561 culture negative EPTB and 45 culture positive EPTB were included. Using culture as reference standard, the overall sensitivities and specificities of Ultra assay were 95.6% (95% CI 84.8 - 99.5) and 97.5% (95% CI 95.8 - 98.6) respectively. Sensitivity and specificity of Ultra for individual category of specimens were also performed. Conclusion: In a low-tuberculosis prevalence setting, Ultra assay confirms to have a good performance in the diagnosis of EPTB for all different extrapulmonary samples.

Background Few data about predictors and outcomes associated with prolonged SARS-CoV-2 RNA shedding (VS) are available. Methods Retrospective study including all patients admitted with COVID-19 in an Italian reference hospital for infectious diseases between March 1 and July 1, 2020. Predictors of viral clearance (VC) and prolonged VS from upper respiratory tract were assessed by Poisson regression and logistic regression analyses. The causal relation between duration of VS and probability of clinical outcomes was evaluated through inverse probability weighted Cox model. Results 536 subjects were included. Median duration of VS from symptoms onset was 18 days (IQR 12-26). The estimated 30-day probability of VC was 70.2% (95%CI:65-75). At multivariable analysis, patients with comorbidities (aIRR = 0.88, p = 0.004), lymphopenia at hospital admission (aIRR = 0.75, p = 0.032) and with moderate/severe respiratory disease (aIRR = 0.42, p 1000 ng/mL at admission (aOR = 1.76, p = 0.035) independently predicted prolonged VS. The achievement of VC doubled the chance of clinical recovery (aHR = 2.17, p

Prophylactic low molecular weight heparin (pLMWH) is currently recommended in COVID-19 to reduce the risk of coagulopathy. The aim of this study was to evaluate whether the antinflammatory effects of pLMWH could translate in lower rate of clinical progression in patients with COVID-19 pneumonia. Patients admitted to a COVID-hospital in Rome with SARS-CoV-2 infection and mild/moderate pneumonia were retrospectively evaluated. The primary endpoint was the time from hospital admission to orotracheal intubation/death (OTI/death). A total of 449 patients were included: 39% female, median age 63 (IQR, 50–77) years. The estimated probability of OTI/death for patients receiving pLMWH was: 9.5% (95% CI 3.2–26.4) by day 20 in those not receiving pLMWH vs. 10.4% (6.7–15.9) in those exposed to pLMWH; p-value = 0.144. This risk associated with the use of pLMWH appeared to vary by PaO2/FiO2 ratio: aHR 1.40 (95% CI 0.51–3.79) for patients with an admission PaO2/FiO2 ≤ 300 mmHg and 0.27 (0.03–2.18) for those with PaO2/FiO2 > 300 mmHg; p-value at interaction test 0.16. pLMWH does not seem to reduce the risk of OTI/death mild/moderate COVID-19 pneumonia, especially when respiratory function had already significantly deteriorated. Data from clinical trials comparing the effect of prophylactic vs. therapeutic dosage of LMWH at various stages of COVID-19 disease are needed.

Iron dysregulation has been implicated in multiple neurodegenerative diseases, including Parkinson’s Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS). One prominent feature of affected brain regions are iron-loaded microglia, but how iron overload influences microglia physiology and disease response is poorly understood. Here we show that microglia are highly susceptible to ferroptosis, an iron-dependent form of cell death. In a tri-culture of human iPSC-derived neurons, astrocytes, and microglia, under ferroptosis-inducing conditions, microglia undergo a drastic shift in cell state, with increased ferritin levels, disrupted glutathione homeostasis, and altered cytokine signaling. Similar ferroptosis-associated signature (FAS) microglia were uncovered in PD, and the signature was also found in a large cohort of PD patient blood samples, raising the possibility that ferroptosis can be identified clinically. We performed a genome-wide CRISPR screen which revealed a novel regulator of ferroptosis, the vesicle trafficking gene SEC24B. A small molecule screen also nominated several candidates which blocked ferroptosis, some of which are already in clinical use. These data suggest that ferroptosis sits at the interface of cell death and inflammation, and inhibition of this process in microglia and other brain cells may provide new ways for treating neurodegenerative disease.

The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts. The core published documents and guidelines have been reviewed including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines. After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities.

Modern field-programmable gate arrays (FPGAs) provide a vast amount of logic resources that can be used to implement complex systems while providing the flexibility to modify the design once deployed. This makes them attractive for software-defined networks (SDNs) applications, and, in fact, most vendors provide the building blocks needed for those applications, which include basic packet classification functions such as exact match, longest prefix match, and match with wildcards. Those are needed for different functions such as routing, security filtering, monitoring or quality of service. The match with wildcards can be done using ternary content addressable memories (TCAMs). TCAMs can be implemented as independent standalone devices or as Internet Protocol (IP) blocks that are used inside networking application-specific integrated circuits (ASICs) such as switching ICs. In both cases, the cells of a TCAM are more complex than that of a normal memory and also than that of a binary content addressable memory (CAMs). This is due to the more complex matching that they need to implement. As FPGAs are used in many different applications, it does not make sense to include TCAM blocks inside them as they would be used only in a small fraction of the systems. Therefore, TCAMs are emulated using the logic resources available inside the FPGA. In recent years, a number of schemes to emulate TCAMs on FPGAs have been proposed, some of them based on the use of the logic resources and others on the use of the embedded memory blocks available on the FPGA. In this brief, a technique to efficiently emulate TCAMs on Xilinx FPGAs is presented. The proposed scheme is based on the use of lookup tables (LUTs) and partial reconfiguration to achieve a more effective use of the FPGA resources while supporting the addition and removal of rules. The proposed scheme has been compared to existing implementations and the results show that it can achieve significant savings in resource usage. In addition, it enables the use of all the LUTs in the device for TCAM implementation, something that is not supported by existing approaches that use LUTRAMs.

Aims This study aims to cast light on immunocytometric alterations in COVID-19, a potentially fatal viral infection with heterogeneous clinical expression and a not completely defined pathophysiology. Methods We studied 35 COVID patients at hospital admission testing by cytofluorimetry a large panel of lymphocyte subpopulations and serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-17A and the soluble receptor of IL-17A (IL-17RA). Key findings At hospital admission, total lymphocytes and most T and B subpopulations were reduced in 50–80% of patients, with close relationship to disease severity. While activated T helper 1 (TH1) and TH17 cells resulted normal or higher. Serum IL-6 was increased in all patients, while TNF-α and IL-17A were higher in advanced stages. A patient subset with low severity had very high IL-17RA levels. Tocilizumab treatment caused an increase of IL-17A in 3/6 patients and a reduction in 3 others, while the lymphocyte number increased in 3 patients and did not change in the others. Significance Cytofluorimetry revealed a functional exhaustion of most lymphocyte populations in COVID patients not involving activated TH1 and TH17. Consequently, there was a relevant cytokines production that contributes to impair the respiratory inflammation. The increase of TH17 and IL-17 in a subset of cases and the evidence of a significant increase of IL-17RA (that prevents the interaction of IL-17 with the cell receptor) in patients with low severity suggest that some patients could benefit from monoclonal antibodies treatment targeting IL-17 pathway. Immunocytofluorimetric markers may contribute to a personalized therapy in COVID patients., Highlights • Total lymphocytes and most T and B sub-clusters were reduced in COVID-19 patients. • Activated TH1 and TH17 cells resulted normal or higher in COVID-19 patients. • Serum IL-6 levels were increased in all patients. • Serum TNF-α and IL-17A were higher in advanced stages. • Evidence of a significant increase of serum IL-17RA in patients with low severity.

A recurring task in security monitoring consists in finding scan-type flows, namely flows which exhibit a large cardinality in terms of number of distinct source/destination addresses, or in most generality packet-level identifiers (e.g. ports, header fields, etc). But cardinality estimation requires to “remember” the identifiers seen in the past, and becomes quite challenging when the goal is to implement per-flow distinct count at wire speed, while maintaining high processing throughput and limited memory footprint. In this demo, we will show how to use HyperLogLog sketches to implement an efficient and innovative top-k cardinality estimation algorithm, called FlowFight. The algorithm has been tested and integrated in a full-fledged software router such as Vector Packet Processor.

In 2015, #FeesMustFall, the largest student movement since the end of the apartheid regime, united with outsourced university workers, in reaction to the neoliberal trajectory of the South Africa higher education system. Based on data collected through extended participant observation and interviews, this chapter analyzes the process of solidarity that emerged between students and workers at the University of Johannesburg and investigates how their unity in action achieved the partial removal of outsourcing labor relations. The processes of solidarity that emerged, drawing from the progressive aspects of a historically determined senso comune, had the potential to question the whole post-apartheid societal structure, obliging the state and the universities’ management to concede remarkable concessions in order to disarticulate this solidarity. This analysis contributes to the debate about limits and potentialities of student and worker movements and their capacity to question the status quo and imagine decolonial alternatives.

Receptor interacting protein kinase 1 (RIPK1) mediates cell death and inflammatory signaling and is increased in multiple sclerosis (MS) brain samples. Here, we investigate the role of glial RIPK1 kinase activity in mediating MS pathogenesis. We demonstrate RIPK1 levels correlate with MS disease progression. We find microglia are susceptible to RIPK1-mediated cell death and identify an inflammatory gene signature that may contribute to the neuroinflammatory milieu in MS patients. We uncover a distinct role for RIPK1 in astrocytes in regulating inflammatory signaling in the absence of cell death and confirm RIPK1-kinase-dependent regulation in human glia. Using a murine MS model, we show RIPK1 inhibition attenuates disease progression and suppresses deleterious signaling in astrocytes and microglia. Our results suggest RIPK1 kinase activation in microglia and astrocytes induces a detrimental neuroinflammatory program that contributes to the neurodegenerative environment in progressive MS.

Purpose: Transient global ischemia arising in human due to cardiac arrest causes selective, delayed neuronal death in hippocampal CA1 and cognitive impairment. Growth arrest and DNA-damage-inducible protein 45 beta (Gadd45b) is a wellknown molecule in both DNA damage-related pathogenesis and therapies. Emerging evidence suggests that Gadd45b is an anti-apoptotic factor in nonneuronal cells and is an intrinsic neuroprotective molecule in neurons. However, the mechanism of Gadd45b pathway is not fully examined in neurodegeneration associated with global ischemia. Methods: Rats were subjected to transient global ischemia by the 4-vessel occlusion or sham operation. The animals were sacrificed at 24 hours, 48 hours, and 7 days after ischemia. The hippocampal CA1 was microdissected and processed to examine mRNA and protein level. To assess neuronal death, tissue sections were cut and processed for Fluoro-Jade and Nissl staining. Results: Here we show that ischemic insults increase abundance of Gadd45b and brain-derived neurotrophic factor, a known target of Gadd45 mediated demethylation, in selectively-vulnerable hippocampal CA1 neurons. We further show that knockdown of Gadd45b increases abundance of a pro-apoptotic Bcl-2 family member Bax while decreasing the antiapoptotic protein Bcl-2, which together promote neuronal death. Conclusions: These findings document a protective role of Gadd45b against neuronal insults associated with global ischemia and identify Gadd45b as a potential therapeutic target for the amelioration of hippocampal neurodegeneration.

In the last decade, a number of frameworks started to appear that implement, directly in user-space with kernel-bypass mode, high-speed software data plane functionalities on commodity hardware. This may be the key to replace specific hardware-based middleboxes with custom pieces of software, as advocated by the recent Network Function Virtualization (NFV) paradigm. Vector Packet Processor (VPP) is one of such frameworks, representing an interesting point in the design space in that it offers: (i) in user-space networking, (ii) the flexibility of a modular router (Click and variants) with (iii) high-speed performance (several millions of packets per second on a single CPU core), achieved through techniques such as batch processing that have become commonplace in high-speed networking stacks (e.g. netmap or DPDK). Similarly to Click, VPP lets users arrange functions as a processing graph, providing a full-blown stack of network functions. However, unlike Click where the whole tree is traversed for each packet, in VPP each traversed node processes all packets in the batch (or vector) before moving to the next node. This design choice enables several code optimizations that greatly improve the achievable throughput. This paper introduces the main VPP concepts and architecture, and experimentally evaluates the impact of its design choices (such as batch packet processing) on its performance.

OBJECTIVES: No study evaluated the contribution of adjunctive surgery in bedaquiline-treated patients. This study describes treatment outcomes and complications in a cohort of drug-resistant pulmonary tuberculosis (TB) cases treated with bedaquiline-containing regimens undergoing surgery.METHODS: This retrospective observational study recruited patients treated for TB in 12 centres in 9 countries between January 2007 and March 2015. Patients who had surgical indications in a bedaquiline-treated programme-based cohort were selected and surgery-related information was collected. Patient characteristics and surgical indications were described together with type of operation, surgical complications, bacteriological conversion rates, and treatment outcomes. Treatment outcomes were evaluated according to the time of surgery.RESULTS: 57 bedaquiline-exposed cases resistant to a median of 7 drugs had indication for surgery (52 retreatments; 50 extensively drug-resistant (XDR) or pre XDR-TB). Sixty percent of cases initiated bedaquiline treatment following surgery, while 36.4% underwent the bedaquiline regimen before surgery and completed it after the operation. At treatment completion 90% culture-converted with 69.1% achieving treatment success; 21.8% had unfavourable outcomes (20.0% treatment failure, 1.8% lost to follow-up), and 9.1% were still undergoing treatment.CONCLUSIONS: The study results suggest that bedaquiline and surgery can be safely and effectively combined in selected cases with a specific indication.

The clinical benefit of convalescent plasma (CP) for patients with coronavirus disease (COVID)-19 is still debated. In this systematic review and meta-analysis, we selected 10 randomized clinical trials (RCTs) and 15 non-randomized studies (total number of patients = 22,591) of CP treatment and evaluated two different scenarios: (1) disease stage of plasma recipients and (2) donated plasma antibody titer, considering all-cause mortality at the latest follow-up. Our results show that, when provided at early stages of the disease, CP significantly reduced mortality: risk ratio (RR) 0.72 (0.68, 0.77), p < 0.00001, while provided in severe or critical conditions, it did not (RR: 0.94 [0.86, 1.04], p = 0.22). On the other hand, the benefit on mortality was not increased by using plasma with a high-antibody titer compared with unselected plasma. This meta-analysis might promote CP usage in patients with early-stage COVID-19 in further RCTs to maximize its benefit in decreasing mortality, especially in less affluent countries., Graphical abstract, Systems medicine; Virology.

Objective To perform a multicenter review of outcomes in patients with H-type tracheoesophageal fistula (TEF) in order to better understand the incidence and causes of post-operative complications. Background H-type TEF without esophageal atresia (EA) is a rare anomaly with a fundamentally different management algorithm than the more common types of EA/TEF. Outcomes after surgical treatment of H-type TEF are largely unknown, but many authoritative textbooks describe a high incidence of respiratory complications. Methods A multicenter retrospective review of all H-type TEF patients treated at 14 tertiary children's hospital from 2002–2012 was performed. Data were systematically collected concerning associated anomalies, operative techniques, hospital course, and short and long-term outcomes. Descriptive analyses were performed. Results We identified 102 patients (median 9.5 per center, range 1–16) with H-type TEF. The overall survival was 97%. Most patients were repaired via the cervical approach (96%). The in-hospital complication rate, excluding vocal cord issues, was 16%; this included an 8% post-operative leak rate. Twenty-two percent failed initial extubation after repair. A total of 22% of the entire group had vocal cord abnormalities (paralysis or paresis) on laryngoscopy that were likely because of recurrent laryngeal nerve injury. Nine percent required a tracheostomy. Only 3% had a recurrent fistula, all of which were treated with reoperation. Conclusions There is a high rate of recurrent laryngeal nerve injury after H-type TEF repair. This underscores the need for meticulous surgical technique at the initial repair and suggests that early vocal cord evaluation should be performed for any post-operative respiratory difficulty. Routine evaluation of vocal cord function after H-type TEF repair should be considered. The level of evidence rating Level IV.

Transient global ischemia arising as a consequence of cardiac arrest in humans causes selective, delayed death of hippocampal CA1 pyramidal neurons and cognitive impairment. Effective treatments to ameliorate the neurodegeneration and cognitive dysfunction associated with global ischemia are an unmet need. Emerging evidence points to a widespread role for microRNAs (miRNAs) as key modulators of target gene expression in neurons. Accordingly, dysregulation of miRNAs are implicated in the pathophysiology of neurodegenerative disease and neurological disorders. Our findings, derived via miRNA-seq, indicate that expression of a subset of microRNAs are altered in postischemic CA1 including miR-34b/c, miR-21, miR-331, miR-181 and miR-29. Ingenuity pathway analysis reveals that miR-34b/c is the leading miR candidate implicated in cell death and survival. A role for miR-34 in the pathogenesis of global ischemia is, as yet, unclear. Here we show ischemia induces p53-dependent activation of miR-34b/c and downregulation of its target genes Bcl-2 and Sirt1, which together promote neuronal death in selectively vulnerable hippocampal CA1 in vivo . Consistent with this, inhibition of miR-34b/c affords neuroprotection, rescues impaired synaptic plasticity and reduces memory deficits in global ischemia. These findings document a causal role for p53-dependent activation of miR-34b/c in neuronal death and identify a novel therapeutic target for amelioration of the neurodegeneration and cognitive deficits associated with ischemic stroke.

In-network computation based on programmable data plane hardware provides a tremendous opportunity to improve throughput, latency and reduce congestion in data center scenarios. However, a judicious use of these network devices must be done based on their limited resources and the specific features of the application to be offloaded. This paper promotes FlowBlaze, a stateful hardware programmable data plane, as a candidate for offloading online MapReduce tasks. Above all, tasks with strict time requirements can benefit from in-network computing since it can significantly lower their latency. Given that MapReduce is a generic programming paradigm, in this paper we first try to identify which subset of MapReduce operations can be transparently offloaded to a specific hardware architecture and which are the limitations of this offloading in terms of memory and computational resources. After, we show how the FlowBlaze architecture can match the partition/aggregation paradigm and we discuss a set of primitives exposed by the FlowBlaze abstraction to perform mapping and aggregation. Finally, we prove the feasibility of this approach applying it to a click-stream analysis use case.

We successfully carried out Europe's first 5G-ready railway trial in an operational environment by combining a passive wavelength-agnostic WDM for optical transport and 60 GHz millimeter-wave for wireless connectivity. The trial achieved multi-Gbit/s seamless connectivity from track-side access points to a fast-moving train.

Bloom filters are widely used in networking to accelerate checks and in particular to avoid accessing slow memories when a match will not be found. Unfortunately, filtering requires several on-chip memory bits per element and thus when the tables are large and the on-chip memory small is not applicable. In those cases, caching the most frequently accessed elements on-chip seems the only viable option. However, the key is typically formed by several packet header fields, which means that each cache entry consumes a significant amount of on-chip memory bits. In this paper, an efficient scheme to cache negatives, that is elements that will not find a match on the table is presented. In more detail, the proposed scheme enables the caching of negatives using less than 16 bits per entry regardless of the size of the key. This translates to a reduction of at least 6x in the size of the cache when used for example flow tracking.

Objective We evaluated the epidemiology and treatment outcomes of multi-drug-resistant (MDR) and pre-extensively-resistant (pre-XDR) tuberculosis (TB) in migrants at two TB reference centers in Italy. Study design Patient selection criteria for the present study were as follows: age ≥18 years, international migrants (i.e., person who lives in a country other than his/her country of origin), MDR or pre-XDR-TB based on drug-susceptibility test findings, full availability of microbiological, radiological and clinical data. Non-intersecting populations between the two centers were selected. The primary outcome was the proportion of patients with a successful (i.e., cured and treatment completed) treatment outcome. Methods A retrospective cross-sectional study was conducted, from 01/Jan/2000 to 01/Jan/2015, at the Regional TB Reference Centre of Lombardy Region, Villa Marelli Institute/ASST Niguarda Ca' Granda (Milan, Italy) and at the Reference Center for MDR-TB and HIV-TB, Eugenio Morelli Hospital ASST (Sondalo, Italy). All data were made anonymous. Qualitative and quantitative variables were collected in an ad hoc electronic database. The statistical software used for all computations was STATA version 15 (StataCorp, Texas, USA). Results Overall, 116 MDR-TB and pre-XDR-TB cases were recorded: 82 (70.7%) MDR-TB and 34 (29.3%) pre-XDR-TB patients, respectively. The majority (53.5%) were from the World Health Organization European Region (excluding EU/EEA) and 75 (64.5%) were male. Median (interquartile range) age was 32 (26–39) years. TB/HIV coinfection was found in 12 (10.3%) patients. Pulmonary TB was diagnosed in 107/116 (92.2%) patients. Resistance to fluoroquinolones and second-line injectables was detected in 22/116 (19.0%) and 12/107 (11.2%) patients, respectively. Overall treatment success was reached in 95/116 (81.9%) cases. Conclusion Pre-XDR-TB in migrants coming from high-endemic countries represents a matter of concern; therefore, prevention and control activities targeted to high-risk populations are needed to progress toward TB elimination.

Offloading to the edge a subset of the cloud services requested by users is a very appealing solution to reduce the bandwidth pressure, minimize latency and improve the overall quality of experience of mobile users. Achieving this goal is technically challenging, since the network functionalities needed to manage this offloading are not trivial, and present significant requirements in terms of scalability and speed. We propose to realize these network functionalities directly in the dataplane, exploiting the characteristic of FlowBlaze, a novel stateful programmable dataplane. Furthermore, we show how the network functions for the traffic offload can be easily expressed using an ad-hoc domain specific language developed for the description of per-flow stateful network functions.

In modern switches, a packet can go through a number of processing steps to determine, for example, if the packet has to be discarded due to security policies, if it needs to be marked for quality of service or to determine the next hop for the packet. Most of those steps can be modeled as a matching of some of the packet fields with a set of rules that are stored in the switch. This has been generalized with the adoption of Software Defined Networks, using for example, the Openflow protocol, on which the processing steps are programmable as table matching operations and defined dynamically by a controller. Implementing this flexible packet matching in a switch is challenging, as we need to support multiple matching tables, each having different key size, and the size of the tables should also be programmable. The main options to support multiple tables are to use different memories for each table or to have several tables share the same memories. In the first approach, each table would have to match the size and width of the memories to achieve an efficient memory usage. This is a severe limitation when flexible table size and entry width need to be supported. In the second approach, all the tables can dynamically share the memories, providing better flexibility. The problem is that the width of the memories needs to be dimensioned to support the largest entry size. This leads to significant memory waste for smaller entries. Hash based techniques like cuckoo hashing can be used to efficiently implement exact matching using standard SRAM memories, and are widely used in modern switches. However, current implementations only support entries of one size. This article presents the Single Double cuckoo hash, which can support elements of two sizes. Its main benefit is to improve memory utilization when multiple tables with entries of different sizes share the same memories. This is achieved at the cost of a small increase in circuit complexity.

The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1–2) and 57 (11.3%) as serious (grade 3–5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.

Fishing communities are facing a variety of challenges including declines in participation, reduced access to fish resources, aging physical infrastructure, gentrification, competition from foreign imports, the &ldquo, graying&rdquo, or aging of their fleets, along with a host of environmental stressors. These factors can represent threats to the continued viability of individual fishing communities. Such communities are clearly in need of tools that will enable them to plan strategically and to be more proactive in charting a sustainable future. This manuscript provides a roadmap for how to engage fishing communities in a bottom-up strategic planning process termed &ldquo, fishing community sustainability planning&rdquo, by describing implementation efforts in four diverse California ports: Morro Bay, Monterey, Shelter Cove, and Eureka. The process draws from the literature on sustainability and community development to assess fishing community sustainability around four broad categories: economics and markets, social and community, physical infrastructure and critical services, environment and regulation. Process steps included developing a project team and community coalition, analyzing baseline data, conducting interviews with waterfront stakeholders, hosting public workshops, and drafting a Fishing Community Sustainability Plan (FCSP) that includes concrete recommendations for how a community&rsquo, s fishing industry and waterfront can be improved. Experiences from the four ports reveal that fishing community sustainability planning can be adapted to a variety of contexts and can contribute tangible benefits to communities. However, there are limitations to what community-scale planning can achieve, as many regulatory decisions that affect communities are enacted at the state or national level. Combining community-level planning with scaled-up fishing community sustainability planning efforts at the state and federal level could help overcome these limitations. FCSP planning is one tool fishing communities should consider as they seek to address threats and plan for their long-term viability.

Objective This study aimed to determine whether switching from low-molecular-weight heparin (LMWH) to unfractionated heparin (UFH) or its continuation in the peripartum affected anesthesia choice or bleeding complications. Study Design A retrospective cohort study of 189 anticoagulated pregnant women who delivered at the University of Illinois at Chicago Hospital and Health Science System from 2005 to 2016. Demography, anesthesia choice, and bleeding complications were compared between the two groups. Results There were 138 (73%) women on LMWH versus 51 (27%) who switched from LMWH to UFH during the peripartum. The demographics were similar, 123 women were on prophylactic: 81 (66%) were on LMWH and 42 (34%) switched to UFH. Of the 66 women on therapeutic anticoagulation, 57 (86%) continued on LMWH, while 9 (14%) switched to UFH. No difference in neuraxial anesthesia type received: 42 (82.4%) versus 108 (79.7%) women (odds ratio: 1.20, 95% confidence interval [CI]: 0.52–2.73, p = 0.837). Bleeding complications more than 1,000 mL, 6 versus 10% (relative risk [RR]: 0.58, 95% CI: 0.17–1.94, p = 0.380) and relaparotomy due to hemoperitoneum, 2% in either group (RR: 0.9, 95% CI: 0.10–8.48, p = 0.930) were similar in the two groups regardless of time of last injection. Conclusion Anesthesia type and rate of bleeding complications were similar between women on LMWH and UFH during the peripartum.

Background The World Health Organization conditionally recommends systematic screening of tuberculosis (TB) and Latent Tuberculosis Infection (LTBI) among asylum seekers (AS) from high-burden countries, but the effectiveness of different screening approaches is controversial. Methods We report the results of a retrospective cohort analysis of TB and LTBI screening among consecutive AS in Brescia, Italy during 2015–2016. TB screening was based on symptoms, LTBI screening on the tuberculin skin test (TST). Logistic regression analysis was performed to identify factors associated with screening uptake. Results Of 2904 registered AS 2567 (88.4%) were evaluated for TB, 62 (2.4%) had symptoms and active TB yield was 155/100,000. Prevalence and incidence TB rates were 545/100,000 persons and 220/100,000 person-years. Questionnaire screening identified 28.6% (4/14) prevalent cases. Of 2303 (89.7%) AS with TST result, the positivity rate was 36.6% (843/2303). Of the 843 candidates for LTBI treatment 413 (49.0%) completed the screening. LTBI treatment was prescribed to 190 (47.9%) of 397 eligible individuals, 10.8% (91) completed treatment. Conclusions TB prevalence and incidence rates were high in this AS population, but symptom-based screening performed poorly. LTBI cascade losses were significant and mainly attributable to the defragmentation of the health care system.

Ternary content addressable memories (TCAMs) are widely used in network devices to implement packet classification. They are used, for example, for packet forwarding, for security, and to implement software-defined networks (SDNs). TCAMs are commonly implemented as standalone devices or as an intellectual property block that is integrated on networking application-specific integrated circuits. On the other hand, field-programmable gate arrays (FPGAs) do not include TCAM blocks. However, the flexibility of FPGAs makes them attractive for SDN implementations, and most FPGA vendors provide development kits for SDN. Those need to support TCAM functionality and, therefore, there is a need to emulate TCAMs using the logic blocks available in the FPGA. In recent years, a number of schemes to emulate TCAMs on FPGAs have been proposed. Some of them take advantage of the large number of memory blocks available inside modern FPGAs to use them to implement TCAMs. A problem when using memories is that they can be affected by soft errors that corrupt the stored bits. The memories can be protected with a parity check to detect errors or with an error correction code to correct them, but this requires additional memory bits per word. In this brief, the protection of the memories used to emulate TCAMs is considered. In particular, it is shown that by exploiting the fact that only a subset of the possible memory contents are valid, most single-bit errors can be corrected when the memories are protected with a parity bit.

Packet classification is an important part of many networking devices, such as routers and firewalls. Software-defined networking (SDN) heavily relies on online packet classification which must efficiently process two different streams: incoming packets to classify and rules to update. This rules out many offline packet classification algorithms that do not support fast updates. We propose a novel online classification algorithm, TupleMerge (TM), derived from tuple space search (TSS), the packet classifier used by Open vSwitch (OVS). TM improves upon TSS by combining hash tables which contain rules with similar characteristics. This greatly reduces classification time preserving similar performance in updates. We validate the effectiveness of TM using both simulation and deployment in a full-fledged software router, specifically within the vector packet processor (VPP). In our simulation results, which focus solely on the efficiency of the classification algorithm, we demonstrate that TM outperforms all other state of the art methods, including TSS, PartitionSort (PS), and SAX-PAC. For example, TM is 34% faster at classifying packets and 30% faster at updating rules than PS. We then experimentally evaluate TM deployed within the VPP framework comparing TM against linear search and TSS, and also against TSS within the OVS framework. This validation of deployed implementations is important as SDN frameworks have several optimizations such as caches that may minimize the influence of a classification algorithm. Our experimental results clearly validate the effectiveness of TM. VPP TM classifies packets nearly two orders of magnitude faster than VPP TSS and at least one order of magnitude faster than OVS TSS.

The challenge addressed in this paper consists in offloading packet-based pacing to a hardware Network Interface Card, while retaining the flexibility of software timers. In this direction, we propose, design, implement, and evaluate a hardware calendar, which can be programmed via a simple yet very flexible programming interface leveraging stateful (adaptive) per-packet timers. We show, for both specific examples (exponential, linearly increasing, etc) as well as for the general case, how to derive such a per-packet timer setting from a high-level desired rate envelope. Further, we describe and evaluate an FPGA implementation which relies on a novel insertion strategy for solving collisions in the calendar’s hash table.

5G networks are called to efficiently and flexibly support an ever growing variety of heterogeneous middlebox-type functions such as network address translation, tunneling, load balancing, traffic engineering, monitoring, intrusion detection, and so on. This flexibility, together with the increasing demands in terms of packet processing throughput, is extremely difficulty to achieve. One of the best candidates to provide such flexibility is a programmable dataplane based on a pipeline of match/action stages, similar to those proposed for Openflow. Designing an high speed programmable dataplane requires to have both flexible and efficient match tables and high speed programmable blocks for action execution. In particular, the most demanding actions, in terms of processing power, are those related to the manipulation of the data inside the packets, i.e. the set of operations (such as encapsulation or header manipulation) performed on packets after the forwarding decision. These encapsulation and header rewriting actions are key elements to put together heterogeneous networks and to enable flexible slicing, as envisioned by the forthcoming 5G network architecture. In the work presented in this paper we focused on the design of a Very Long Instruction Word (VLIW) processor, based on a custom instruction set, able to perform efficient packet processing operations granting multi-Gbps throughput. In particular, we provide details of the Packet Manipulator Processor (PMP) architecture and its I/O interfaces, which have been designed to accomplish packet manipulation tasks, we discuss the throughput analysis of three use cases (tunneling, NAT, and ARP reply generation) and present FPGA synthesis results.

As applications and user requirements are constantly evolving, there is a need to provide flexible networks that are able to process packets at high speed. One of the basic functions used for packet processing is matching a key formed by some fields of the incoming packet header against a set of stored rules. This is done for example to determine the next hop of a packet or to apply security checks on a firewall. In many cases, the stored rules have do not care bits as that enables a more flexible and compact representation of the rules. Therefore, the matching can be done in hardware using Ternary Content Addressable Memories (TCAMs). However, TCAMs pose several problems in many implementations. For example, for ASICs they require much more circuit area and power than standard SRAMs. On the other hand, designs based on programmable logic such as Field Programmable Gate Arrays (FPGAs) can only use the blocks provided by the FPGA that do not typically include TCAMs. In this last case, a TCAM can be emulated using the FPGA logic resources but with a large cost. To reduce the cost of implementing TCAMs, a number of algorithmic solutions have been proposed and are known as Algorithmic TCAMs or A-TCAMs. Most of those schemes target either software or ASIC implementations. In this paper we present Multiple Hash Matching Units (MHMU) an A-TCAM solution targeted towards FPGA implementations. The proposed scheme exploits the massive parallelism of FPGAs to implement many hash based matching units that use the embedded block RAM memories of the FPGA. The proposed MHMU scheme has been mapped to a Xilinx series 7 FPGA to check its efficiency in terms of resource usage and its scalability. To validate the effectiveness of MHMU, a simple configuration has been tested with Classbench generated sets of rules. The results show that the MHMU is able to consistently accommodate sets with several tens of thousands of rules with large keys.

Laparoscopic cholecystectomy is the most common procedure performed by general surgeons in the United States, with approximately 600,000 procedures performed annually. As the cost of care rises, there is increasing emphasis on utilization and quality. Our objective was to evaluate the cost of laparoscopic cholecystectomy in our health system and to compare the operative times and outcomes at high- and low-cost centers. We evaluated all laparoscopic cholecystectomies performed in our system over a 1-year period. The operating room supply costs and procedure durations were obtained for each of the hospitals. The American College of Surgeons National Surgical Quality Improvement Program outcomes and demographics were compared to the costs for each hospital. During the study period, 7601 laparoscopic cholecystectomies were performed at 20 hospitals (170–759/hospital) by 227 surgeons. The average cost per case ranged from $296 at the lowest cost center to $658 at the highest cost center. The average operative time varied between sites from 46 to 95 min. There was no association between cost and operative time or case volume. There was a slight trend toward increased cost with higher number of emergency procedures, but this was not well correlated (R2 = 0.03). The patient demographics and comorbidities were similar between sites. There were no significant differences in postoperative complications between high- and low-cost centers. The items with the greatest increase in cost were disposable trocars, disposable hook cautery, disposable endoscissors, and disposable clip appliers. We estimate that a savings of over $300/case is possible by using reusable instruments, which would result in an annual savings of $1.3 million for our health system, and $285 million nationwide. Performing laparoscopic cholecystectomy with reusable instruments can significantly decrease costs and does not increase operative time or postoperative complications.

In the last decade, a number of frameworks started to appear that implement, directly in user-space with kernel-bypass mode, high-speed software data plane functionalities on commodity hardware. Vector Packet Processor (VPP) is one of such frameworks, representing an interesting point in the design space in that it offers: (i) in user-space networking, (ii) the flexibility of a modular router (Click and variants) with (iii) the benefits brought by techniques such as batch processing that have become commonplace in lower-level building blocks of high-speed networking stacks (such as netmap or DPDK). Similarly to Click, VPP lets users arrange functions as a processing graph, providing a full-blown stack of network functions. However, unlike Click where the whole tree is traversed for each packet, in VPP each traversed node processes all packets in the batch before moving to the next node. This design choice enables several code optimizations that greatly improve the achievable processing throughput: the purpose of this demonstration is to introduce the main VPP concepts and architecture, as well as experimentally showing the impact of design choices- and especially of batch packet processing-, on the achievable packet forwarding performance.

Background Barriers to access medical screening and care may underestimate the number of diseased subjects among immigrant populations. Aims To evaluate the prevalence of human immunodeficiency virus, hepatitis B virus and hepatitis C virus infections among immigrants recruited in a disadvantaged area. Methods The study enrolled all subjects seen between 1999 and 2009 at an on-site health and family counselling centre for immigrants. During the first 6 years of the study a pro-active recruitment was performed using a mobile unit. Results Overall 2681 subjects were enrolled (median age: 31 years; 52.8% males; 82.3% from Sub-Saharan Africa; 13.9% of the women were sex workers). A total of 206 subjects (7.6%) were hepatitis B surface antigen-positive, 84 (3.6%) were anti-hepatitis C virus-positive, 129 (5%) were anti-human immunodeficiency virus-positive, 84 (3.1%) were drug users, and 436 (16.3%) were alcohol abusers. The prevalence of hepatitis B surface antigen and anti-hepatitis C virus remained consistent throughout the study period, while the prevalence of human immunodeficiency virus significantly decreased. At multivariate analysis, hepatitis B virus infection was associated with male gender, hepatitis C virus infection with drug addiction, and human immunodeficiency virus infection was associated with female gender, drug addiction, and active recruitment. Conclusions An active recruitment strategy should be considered to reach disadvantaged populations at high risk of human immunodeficiency virus infection.

The mammalian genome pervasively transcribes a variety of functional noncoding transcripts, including the recently discovered long noncoding RNAs (lncRNAs). LncRNAs play major roles in regulating gene expression in mammals, but their expression and functions in the post-stroke brain remain largely unknown. Using a mouse model of transient focal ischemia, we applied RNA-sequencing to evaluate for the first time the unbiased, genome-wide expression of lncRNAs as a function of reperfusion time in the cerebral cortex. A 1h middle cerebral artery occlusion was conducted in adult male mice and ipsilateral cortices were harvested at 6h, 12h or 24h of reperfusion. RNA was isolated and used for Illumina sequencing. The reads were assembled and mapped to mouse reference genome GRCm38/mm10 and differential expression between the groups was evaluated using TopHat-Cufflinks. We observed that the baseline expression of lncRNAs in the healthy cortex was low, but hundreds of lncRNAs were highly altered after stroke. We identified 1311 isoforms at 6h (1146 upregulated; 165 downregulated), 1287 isoforms at 12h (954 upregulated; 333 downregulated), and 1090 isoforms at 24h (907 upregulated; 183 downregulated) of reperfusion that were significantly altered (absolute fold-change ≥ 2; q-value

Stateful programmable dataplanes are emerging as a disruptive technology and an enabler factor for network function virtualization in SDN environments. In this demo paper we show three real world use cases with stateful forwarding requirements to validate both the hardware and software implementations of the Open Packet Processor data plane.

We introduce a new hardware/software platform for testing SRAM-based FPGAs under heavy-ion and neutron beams, capable of tracing the bit-flips in the configuration memory back to the physical resources affected in the FPGA. The validation was performed using, for the first time, the neutron source at the RALILSIS facility. The ISlS beam features a 1/E spectrum, which is similar to the terrestrial one with an acceleration between 107 and 10 8 in the energy range 10-100 MeV. The results gathered on Xilinx SRAM-based FPGAs are discussed in terms of cross section and circuit-level modifications. © 2007 IEEE.

Security of today's networks heavily rely on network intrusion detection systems (NIDSs). The ability to promptly update the supported rule sets and detect new emerging attacks makes field-programmable gate arrays (FPGAs) a very appealing technology. An important issue is how to scale FPGA-based NIDS implementations to ever faster network links. Whereas a trivial approach is to balance traffic over multiple, but functionally equivalent, hardware blocks, each implementing the whole rule set (several thousands rules), the obvious cons is the linear increase in the resource occupation. In this work, we promote a different, traffic-aware, modular approach in the design of FPGA-based NIDS. Instead of purely splitting traffic across equivalent modules, we classify and group homogeneous traffic, and dispatch it to differently capable hardware blocks, each supporting a (smaller) rule set tailored to the specific traffic category. We implement and validate our approach using the rule set of the well-known Snort NIDS, and we experimentally investigate the emerging trade-offs and advantages, showing resource savings up to 80 percent based on real-world traffic statistics gathered from an operator's backbone.

The On-Q(®) pain pump provides a continuous infusion of local anesthesia for management of postoperative pain. The objective of this study was to assess the efficacy and outcomes of the On-Q(®) pump compared to continuous epidural in children postoperatively.We performed a retrospective review of patients in our hospital who received a postoperative epidural or On-Q(®) pump from 2005 to 2008. Patients were sub-categorized by incision type.Seventy patients received epidural and 66 On-Q(®). On-Q(®) therapy was longer by 1 day (p0.0001), but did not affect postoperative length of stay. Patients with On-Q(®) pumps had a decreased rate of Foley catheter placement (p = 0.002) and shorter duration of catheter use by more than a day (p0.001). Moderate to severe pain was similar in the two groups on postoperative days 0-5. Supplemental narcotic use was higher in the On-Q(®) group only on postoperative day 1 (p = 0.005) and in patients with midline and transverse abdominal incisions. No differences were seen in time to ambulation or recovery of postoperative ileus.The On-Q(®) pain pump is an effective method for postoperative pain control, without the inherent risks of epidural catheters.

Soft errors that corrupt the value of bits stored in registers or memories are a major issue for modern electronic systems. To ensure that they do not cause failures, error detection and correction codes are commonly used to protect memories. When memories are used for a specific application, sometimes it is possible to optimize the protection based on the knowledge of the application. One example is the memories used in network devices for packet processing. In particular, the protection of approximate membership check structures such as Bloom filters has been recently studied showing that it is possible to optimize the protection. Cuckoo filters are an alternative to Bloom filters for approximate membership check that has been recently proposed. Cuckoo filters are interesting as they are competitive in terms of memory usage for low false positive rates and also support the removal of elements. In this paper, the protection of Cuckoo filters against soft errors is studied showing that it can be enhanced by exploiting its structure and using the knowledge of the effects on an error in a Cuckoo filter.

In this paper we show how to realize a per-flow QoS (Quality of Service) policy based on the token bucket algorithm using OPP (Open Packet Processor), a recently proposed stateful programmable dataplane. OPP is configured as a switch that enforce a token bucket policy independently on each flow processed by the switch controlling their bandwidth and burstiness. The paper shows the design of the token bucket algorithm using the extended finite state machine (EFSM) abstraction provided by OPP and discusses the details of the implementation carried out using a proof-of-concept FPGA prototype of the OPP pipeline.

This paper presents a method to implement complex tasks into stateful SDN programmable dataplanes. In particular, the presented method proposes to use the internal microcontroller typically used to configure the programmable dataplane also to perform some complex operations that do not require to be executed on each packet. These operations can be executed on a set of data gathered by the dataplane and processed in a time scale that is much higher than the time window of a packet, but is much less than time scale needed for an external SDN controller. Moreover, the use of the configuration microcontroller instead of an external SDN controller to avoid the exchange of data on the control links permits a fine grain tuning of the operations to perform from the timing point of view (precise timestamping, low latency etc.). A set of measurements showing the feasibility of the method are presented, and a simple use case is described to show the effectiveness of this method to enhance the capability of stateful programmable dataplanes.